Teriflunomide
| Evidence Level: L1 | Predicted Indications: 1 |
Table of Contents
Teriflunomide: Predicted Indication of Relapsing-Remitting Multiple Sclerosis
One-Sentence Summary
Teriflunomide is an oral immunomodulator that limits lymphocyte proliferation. The TxGNN model predicts it may be effective for relapsing-remitting multiple sclerosis (RRMS), with 28 clinical trials and 19 publications supporting this direction. The drug is already a marketed disease-modifying therapy for relapsing MS, so this result validates the model rather than revealing a new repurposing signal.
Quick Overview
| Item | Content |
|---|---|
| Predicted New Indication | Relapsing-remitting multiple sclerosis |
| TxGNN Prediction Score | 99.24% |
| Evidence Level | L1 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 licenses (NDA and ANDA combined) |
| Recommended Decision | Proceed with Guardrails |
The US license records contain no approved-indication text, so the original indication could not be extracted from the local data.
Why is This Prediction Reasonable?
Teriflunomide is the active metabolite of leflunomide. It selectively and reversibly inhibits the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH). This blocks de novo pyrimidine synthesis and reduces the proliferation of activated T and B lymphocytes.
RRMS is driven by autoimmune, lymphocyte-mediated inflammation of the central nervous system. Limiting the expansion of activated lymphocytes is therefore a plausible and well-established mechanistic fit. Trial NCT02833714, for example, studies B-cell effects of the drug in RRMS patients.
The Evidence Pack lists no original indications, and the mechanism-of-action field was empty. This looks like a data-completeness gap rather than a true absence. Multiple randomized phase 3 trials and reviews already treat teriflunomide as an established first-line oral therapy for relapsing MS.
Clinical Trial Evidence
The pack lists 28 trials. The 10 most relevant are shown below.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00134563 | Phase 3 | Completed | 1088 | Double-blind, placebo-controlled pivotal trial of teriflunomide on relapse frequency and disability accumulation in relapsing MS |
| NCT00883337 | Phase 3 | Completed | 324 | Rater-blinded comparison of two teriflunomide doses versus interferon beta-1a, with long-term extension |
| NCT00803049 | Phase 3 | Completed | 742 | Long-term extension documenting safety of teriflunomide 7 mg and 14 mg in relapsing MS |
| NCT00228163 | Phase 2 | Completed | 147 | Long-term safety and efficacy extension of the phase 2 teriflunomide study |
| NCT04788615 | Phase 3 | Completed | 185 | Ofatumumab versus physician’s-choice first-line DMT in newly diagnosed relapsing MS (teriflunomide is a possible comparator) |
| NCT01881191 | N/A | Completed | 50 | 12-month MRI study of teriflunomide effects on gray matter pathology |
| NCT06843382 | N/A | Not yet recruiting | 100 | Real-world comparison of teriflunomide and dimethyl fumarate on physical and cognitive fatigability |
| NCT02490982 | N/A | Completed | 106 | Observational study of teriflunomide effectiveness in RRMS over at least 2 years |
| NCT03302442 | N/A | Completed | 3000 | Observational comparison of dimethyl fumarate and teriflunomide on clinical and MRI outcomes in RRMS |
| NCT02776072 | N/A | Completed | 2978 | Retrospective real-world outcomes for RRMS patients on Tecfidera, Copaxone, Aubagio or Gilenya |
Literature Evidence
The pack lists 19 publications. The 10 most relevant are shown below, with randomized trials first.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 32757523 | 2020 | RCT | N Engl J Med | Ofatumumab versus teriflunomide in MS, with teriflunomide as the active oral comparator |
| 36001711 | 2022 | RCT | N Engl J Med | Ublituximab versus teriflunomide in relapsing MS |
| 33779698 | 2021 | RCT | JAMA Neurol | OPTIMUM: first phase 3 head-to-head of two oral DMTs, ponesimod versus teriflunomide |
| 39307151 | 2024 | RCT | Lancet Neurol | Two phase 3 trials of evobrutinib against teriflunomide as active comparator |
| 40202623 | 2025 | RCT | N Engl J Med | Tolebrutinib versus teriflunomide in relapsing MS |
| 38174776 | 2024 | Network meta-analysis | Cochrane Database Syst Rev | Compares immunomodulators and immunosuppressants for RRMS; each reduces relapses and slows disability versus no treatment |
| 31898276 | 2020 | Meta-analysis | CNS Drugs | Narrative review of efficacy and safety of five oral RRMS therapies, including teriflunomide |
| 37528262 | 2023 | Meta-analysis | Neurotherapeutics | Real-world comparison of dimethyl fumarate and teriflunomide in RRMS |
| 31098896 | 2019 | Review | Drugs | Teriflunomide is an effective and generally well-tolerated treatment for relapsing MS, based on RCTs and real-world data |
| 37382446 | 2023 | Review | Expert Rev Neurother | Teriflunomide as first-line oral therapy in pediatric RRMS, recently approved in the EU |
Most of the RCTs above use teriflunomide as the active comparator for newer agents. They show it is the established standard of care, but they are not evidence of its own efficacy versus placebo. That evidence comes from the pivotal trial NCT00134563.
US Market Information
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| NDA202992 | Aubagio | Tablet, film coated | Genzyme Corporation |
| ANDA209700 | Teriflunomide | Tablet, film coated | AvKARE |
| ANDA209702 | Teriflunomide | Tablet, film coated | Mylan Pharmaceuticals Inc. |
| ANDA218663 | Teriflunomide | Tablet, film coated | Concord Biotech Limited |
The pack reports 20 licenses in total, and only these four distinct authorizations are shown. The route of administration is oral.
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Two or more completed phase 3 RCTs (NCT00134563, NCT00883337), a phase 3 long-term extension, and many reviews and comparator trials support teriflunomide in relapsing MS. The drug is already marketed, so the prediction is a validation of the model. The package insert, warnings and mechanism-of-action data are still missing from the pack.
To proceed, the following is needed:
- Package insert warnings and contraindications, currently a blocking gap. Standard monitoring should cover hepatotoxicity, teratogenicity and use of the accelerated-elimination procedure.
- Approved-indication text for the US licenses, to confirm the label status of relapsing MS.
- Mechanism-of-action and original-indication fields from DrugBank, to complete the record.
- Drug-interaction data, as the query returned no results.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.